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Insulin-like growth factor 1(IGF-1) signaling pathway has been suggested as an important oncogenic mediator in various malignancies, including lung cancer. In this study, we aimed to evaluate serum levels of IGF-1, IGF-2 and IGF-Binding Protein 3 (IGF-BP3) before and after chemotherapy or chemoradiotherapy treatment in patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) and their potential correlation with response to therapy and patient survival.

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Methods

Seventy-three patients with stage III/IV NSCLC were included in the study. Expression of IGF1, IGF2, and IGFBP3 was evaluated in peripheral blood samples in two separate time points, at baseline and 3 months post treatment. Analysis and quantification of circulating levels of IGF-1, IGF-2, IGF-BP3 were performed by total ELISA technique. IGF-1/IGF-BP3 ratio is considered an indicator of IGF-1 bioavailability.

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Results

In univariate analysis, the median value of IGF-1 after treatment (130.80 vs 98.00 ng/ml, p = 0.087), and the median ratio of IGF-1/IGF-BP3 (0.01044 vs 0.00678, p = 0.056) were higher in responders. Further analysis of the variation of each biomarker before and after treatment showed that the median value of IGF-1 was decreased after treatment in the total population (125.82 from 133.4 ng/ml, p = 0.087), albeit no difference was found between subgroups. In addition, the median value of IGF-1/IGF-BP3 ratio was found to be lower after treatment in the total population (0.01006 from 0.01252, p = 0.011). Importantly, the post-treatment value of the ratio was significantly reduced in responders (0.01044 from 0.01255, p = 0.02). No correlation was found between variation in biomarker values, patient OS and PFS.

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Conclusions

In a cohort of patients with stage III/IV NSCLC treated with chemotherapy or chemoradiotherapy, reduction of IGF-1/IGF-BP3 ratio, which is an indicator of IGF-1 bioavailability, was statistically significant in patients that responded to treatment. If validated in larger cohorts, our results support the use of IGF-1/IGFBP3 as a predictive tool for response to chemotherapy in NSCLC.

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